On a typical day, we encounter any number of control
systems—devices that regulate the behavior of other devices: the
cruise control in our cars, which maintains the vehicle's speed
whether it is going uphill or downhill or there's a headwind; or the
thermostat in our homes, which maintains the temperature inside
regardless of how hot or cold it is outside. And there are the
biological control systems in the cells of our bodies, such as those
that—if everything is functioning as it should—maintain our blood
sugar within a certain range regardless of what we eat or whether
our stomachs are full or empty.

Control systems are Bill Messner's specialty. He has worked on
controls for data storage and robotic systems, and in recent years,
he has begun to apply his work to biological research. “The interest
that I have in this area is twofold,” says Messner, the acting chair
of the Department of Mechanical Engineering.* “One is building
instrumentation to probe blood cells, tissues, and maybe other
things—for examining the biological system. And the other thing is
to see what the biological system itself is doing. So we build
control systems for the instruments and then we also are interested
in how the biological systems control themselves.”

What Messner is now trying to understand, more specifically, is
how cells and tissues respond to chemical stimuli. To that end, he
is designing and building instruments that can be used to
investigate the mechanics of cells using microfluidics.

A biological controls system experiment with microfluidics goes
something like this: Researchers place pieces of frog embryo in
microfluidic channels, which are very small pipes about a millimeter
wide or even narrower. Because the channels are narrow, fluids that
flow down them don't mix. Instead, they stay in separate lanes,
flowing side by side. As a result, researchers can treat different
parts of the embryo with different chemicals; and by changing the
flow rates of the chemicals, they can move what they call the
“interface” between them, so that part of the embryo always gets
stimulus, part never gets stimulus, and the part in the middle is
stimulated on and off.

To do this, scientists would use a syringe pump. The trouble is that
the amount of liquid a syringe can hold is limited, and it is
difficult to control flow rates accurately inside the channels. That
meant researchers could only do these microfluidic experiments
slowly and only as long as the amount of chemical in the syringe
lasted. One of the systems Messner helped devise is a new control
mechanism that lets researchers manipulate the fluids more
precisely, very quickly, and on the scale of hours, days, or even
weeks. The innovation was to replace the syringe pump with a coupled
variable resistance and squeeze pump, allowing researchers to use a
supply of fluid from a “reservoir of essentially arbitrary
size—gallons, in fact we could use a swimming pool,” Messner says.

“That's a huge reservoir we can run for a long time,” he explains.
“But we've also got this mechanism that allows us to change things
really fast, faster than once per second, like probably closer to 10
times per second. That capability is very, very handy for doing the
kind of experiments we like to do because we don't have to wait very
long for moving this interface across the embryo or tissue. We can
almost instantly move the interface from one side to the other. So
we know very precisely how long a particular part of the tissue has
been stimulated.” Eventually, he says, knowledge about how
biological systems respond to stimuli and control themselves might
help scientists develop human therapies to facilitate wound healing
or arrest or slow down the growth of cancer.

At Tufts School of Engineering, “Messner's work in applying
control theory to biological systems will be a strong addition to
our department's current activities in dynamics, controls, and
sensor systems,” Robert J. Hannemann, formerly the acting chair of
the mechanical engineering department and director of Tufts Gordon
Institute, observes, “especially in our collaborative research in
soft-body robotics and the new IGERT program in this area.” Messner
says he's particularly excited to partner with biomedical engineer
and Chair David Kaplan, co-PI of that program, as well as Michael
Levin, director of the Tufts Center for Regenerative and
Developmental Biology.

“Mike has done just amazing stuff. I'm really hoping that I will
be able to collaborate with him and be a part of his research on
embryonic development—and I think where I will jump in, at least
initially, is helping him to create the instrumentation to do more
sophisticated experiments that he's already started doing,” says
Messner. “Definitely the biology is kind of the hot thing for me
right now. It's got a lot going on at Tufts, great collaborators,
and technologies that allow us to have capabilities that formally
were very difficult or impossible.”

*Dr. Bill Messner is currently acting chair and visiting
professor. He will be instated as chair of Mechanical Engineering
pending approval by the Tufts University Trustees.

Heather Wax is a science writer living in Brookline. She has
written for Scientific American, Ode, The
Boston Globe, and MIT's Technology Review, among other
publications.